Blood Pressure Management in Acute Stroke



Optimal Management of Blood Pressure in Acute Stroke

Patrick Melanson, MD

Introduction

The optimal management of blood pressure following acute stroke is controversial. Persistent, marked elevation of BP can promote hemorrhage, increase cerebral edema, and raise ICP. However, acutely decreasing BP may lead to hypoperfusion and cerebral ischemia. In many cases of acute neurologic illness, systemic hypertension is a reflex response to a decrease in cerebral perfusion pressure and should be treated conservatively, if at all. There are no large randomized controlled trials in the medical literature that addresses the question of BP management following acute stroke. Thus, decisions on BP control must be based upon our current understanding of cerebral physiology, pathophysiology, and pharmacology, recognizing that this knowledge has been gleaned from basic science research, animal studies, and small human studies. Unfortunately, the results of these studies are sometimes contradictory.

Chronic Hypertension

Chronic hypertension is the most prevalent cardiovascular disorder in North America and is the leading cause of cardiovascular and cerebrovascular morbidity and mortality. It is one of the most important risk factors for stroke. The importance of long-term BP control is well recognized and has become a cornerstone of primary stroke prevention. A sustained reduction of hypertension over several years results in a marked reduction in the occurrence of a first stroke. While the benefits of treating chronic hypertension are firmly established, one cannot extrapolate from long-term treatment and BP control to the acute situation. The risks and benefits of treating acute increases in BP after an acute neurologic event are much less clear.

Cerebrovascular physiology

Since neurons are highly dependent on adequate substrate delivery in order to maintain viability, cerebral blood flow (CBF) is tightly controlled. The brain maintains a constant CBF at approximately 50 ml/100gm/min despite large changes in perfusion pressure. When BP increases, cerebral vessels constrict and cerebral vascular resistance (CVR) increases in order to maintain a constant flow. When BP decreases, or ICP increases the vessels dilate and CVR decreases to keep CBF constant. The normal range of cerebral autoregulation is a mean arterial pressure (MAP) of 50 to 150 mmHg in normotensive individuals. When blood pressure falls below the lower limit of autoregulation, cerebral blood flow becomes completely dependant on cerebral perfusion pressure (CPP) and thus systemic blood pressure as the blood vessels are already maximally dilated and CVR is at its minimum. Therefore further decreases in BP will result in decreases in cerebral blood flow and render neurons ischemic.

- CBF = CPP/ CVR

- CPP = MAP – ICP

- MAP = Diastolic Pressure + 1/3 Pulse Pressure

There are many acute neurologic diseases and chronic conditions that result in impaired cerebral autoregulation. When autoregulation is impaired, CBF becomes completely dependent on CPP and all changes in systemic BP result in changes in CBF. This means that if BP is decreased then cerebral blood flow will decrease as well. Thus the potential exists for a drop in systemic blood pressure to result in increased cerebral ischemia. Acute ischemic and hemorrhagic CVA’s have been shown to adversely effect cerebral autoregulation and make the brain more vulnerable to decreases in BP. One way the brain protects itself is by a reflex increase in MAP that will counteract any decrease in CPP when ICP increases. In other words, elevations in BP following an acute neurologic event are often reflex responses aimed at maintaining adequate CBF to neurons. Lowering systemic BP by pharmacological means in this situation could theoretically increase brain ischemia. Furthermore, many studies have shown that the autoregulation curve is right shifted in chronic hypertensives with the range of autoregulation typically 120 to 160. The lower limit has been found to be 113 in a group of poorly controlled hypertensives and 96 in well controlled hypertensives. In normotensive patients the lower limit has been found to be as high as 73 mmHg. The capacity to regulate cerebral blood flow is also reduced in elderly patients.

Practically speaking, this means that there are many reasons why a patient with an acute stroke may require a higher BP than normal to maintain adequate perfusion to injured regions of brain. Lowering systemic BP could result in further cerebral ischemia. There are no means presently available to determine to which level lowering BP to is safe. It would seem prudent to err on the side of a higher BP when making treatment decisions.

Ischemic Stroke

It appears that acute elevations in BP are common after an acute ischemic stroke, but in the majority of patients BP returns to baseline levels within several days without treatment. Approximately 80% of patients with acute stroke have elevations of BP on admission to hospital even though only 1/3 have a history of hypertension. This elevation is generally more marked in chronic hypertensives and tends to decrease spontaneously over the first 7 days post-event with the greatest decline in the first 24 hours and in those with the highest values. Ten days after an ischemic stroke two-thirds of patients are normotensive.

Some studies have shown early increased mortality in those patients with increased BP, but a cause and effect relationship has not been established. There is no convincing evidence that acute hypertension in itself has a deleterious effect on the outcome during the acute phase of cerebral infarction. The questions that needs to be addressed is whether this transient increase in BP changes morbidity or mortality, whether it requires reduction in the acute phase, and if so, with what agent.

In patients with acute ischemic stroke there is good evidence to believe that there is a portion of viable brain surrounding the zone of dense ischemia that is dependent on maintenance of CPP to preserve CBF. When an artery is occluded, a central core of severe ischemia is produced, surrounded by a zone with less reduction in blood flow where perfusion is maintained by collateral circulation. Flow through these dilated collateral vessels is dependent on CPP; thus a reduction in MAP can result in a large increase in the size and severity of the zone of ischemia. The pathophysiologic state that occurs in acute ischemia in which neurons are nonfunctional but alive and salvageable by reperfusion has been called the ischemic penumbra.

On the other hand, there are also several theoretical benefits to lowering BP. These include reducing edema formation, lessening the risk of hemorrhagic transformation (especially in anticoagulated patients), and preventing further vascular damage. However, a reduction in BP has not been shown to decrease edema and may actually worsen it by causing further ischemia. Since edema is a result of ischemia, if reducing CPP worsens ischemia, then edema may worsen as well. Neurologic deterioration due to hemorrhagic transformation is a rare complication of acute anticoagulant treatment of ischemic stroke. Some reports suggest that this risk is increased in hypertension, but this is not consistent. Any role for reduction of BP to reduce the risk of hemorrhage remains conjectural (plus there is no evidence to support early heparinization). The only definite link between hemorrhagic transformation and systemic HTN is in cases of either coronary or cerebral thrombolysis in which the risk of cerebral hemorrhage is significantly increased. Hypertension should be treated prior to initiating thrombolytic therapy.

Intracerebral hemorrhage

Although there is a clear relationship between chronic hypertension and intracerebral hemorrhage the relationship between acute elevation of BP and ICH remains unclear. Again, no randomized controlled trials have been performed that would allow clear clinical guidelines to be drawn up. The major rationale for lowering BP acutely is that early rebleeding or progression of hematoma size may be important causes of morbidity and death, and rebleeding may be related to acute or chronic hypertension. However, no clear causal relationship between BP elevation and risk of rebleed has been demonstrated to date. In fact, several studies have concluded that there is little evidence that acute hypertension provokes rebleeding in ICH. Poorly controlled hypertension may be associated with increasing hematoma size but this is not necessarily causal. Furthermore, it has not been demonstrated that lowering BP decreases the risk of rebleeding or improves outcome.

The pathophysiology of ICH is complex. There is definite physical disruption produced by the hematoma. However, local tissue pressure produces a zone of ischemia surrounding the clot and CBF levels in this region may be close to or below the levels required to maintain neuronal viability. The clot is a space-occupying lesion that often leads to an increase in local ICP. Generalized increases in ICP may further impair CPP and CBF both locally and in more distant sites. Animal models have demonstrated both impaired autoregulation and decreased CBF following ICH. As with acute ischemic stroke there is scientific basis for believing that reductions in arterial pressure will further impair CBF and lead to worsening of ischemic damage. For these reasons, it is logical to assume that any decrease in systemic BP will compromise cerebral perfusion and that treatment should be aimed at decreasing ICP rather than reducing systemic BP directly.

At present recommendations are therefore arbitrary. Although there is no BP value that is proven to be too high, when MAP reaches 145 to 150, many physicians believe the risk of rebleeding and cerebral edema is too high. If the BP is to be reduced, it should be done cautiously to a MAP of 140 to 145.

ANTIHYPERTENSIVE THERAPY

The ideal antihypertensive agent would be one that does not adversely impair cerebral autoregulation, increase ICP or decrease cerebral perfusion. It should be easily titratable and have a short half-life of action. Nitroprusside, nitroglycerine, calcium channel blockers, and hydralazine are direct acting cerebral vasodilators that can impair autoregulation, increase ICP, and may decrease CBF. Alpha and beta-blockers, ganglionic blockers, and ACE Inhibitors have little effect on resting blood flow and shift the autoregulatory curve downward.

Antihypertensives can be divided into three categories;

1) Antihypertensives best avoided- nitroprusside, nitroglycerine, hydralazine,

These agents are direct arteriolar or venous vasodilators. Vasodilation can increase cerebral blood volume and thus lead to increased ICP. They can also lead to systemic salt and water retention due to peripheral vasodilatation and thus increase cerebral edema.

Nifedipine has the potential to cause precipitous, rather uncontrollable decreases in systemic BP, and consequently CPP, when given sublingually.

2) Recommended antihypertensives – labetalol, beta-blockers, ACEI, clonidine

These agents do not act directly on cerebral blood vessels and do not adversely effect cerebral autoregulation nor do they increase ICP.

Labetalol is the usual first line agent used to treat hypertension in neurological illness. It is given at starting doses of 5 to 10 mg iv q10 minutes until the desired effect is achieved.

ACE inhibitors are acceptable second line agents. Enalaprilat can be given iv or captopril can be given sublingually at 12.5 to 25 mg.

Clonidine is not available intravenously in North America and the oral form takes hours to days to achieve adequate effect, thus relegating it to a third line agent.

3) Drugs to be used with caution - nicardipine, nifedipine ( Calcium Channel Blockers)

Some evidence to suggest a neuroprotective effect when CCB are given post-stroke, SAH, or trauma but these beneficial effects were seen in patients in whom the BP did not decrease more than 10% from baseline levels. CCB are direct acting vasodilators and have been shown to increase CBF and ICP.

Blood Pressure Management: Conclusions and Recommendations

1) In almost all cases of acute neurological illness, systemic hypertension is a reflex response to a decrease in cerebral perfusion pressure and should be treated conservatively if at all.

2) Clinical and experimental evidence indicates that reductions in BP carry a risk of producing further ischemic brain damage in patients with ischemic stroke and ICH.

3) In the absence of hypertensive encephalopathy or systemic cardiovascular emergency requiring immediate BP reduction (AMI, unstable angina, aortic dissection), the benefits to be derived from immediately or acutely lowering systemic BP in patients with an acute stroke of any kind remain conjectural and unsupported by good clinical or experimental studies.

4) Designation of any level of elevated BP as too high or prescription of any degree of BP reduction as desirable cannot be supported by existing data.

5) If conditions other than the stroke require BP reduction, then that should be done carefully under close clinical observation. Preparations should be made to rapidly return the BP to pre-existing levels in the event neurologic deficits appear.

6) Cerebral vasodilators should be avoided in patients with suspected or proven increases in ICP.

Ischemic Stroke

1) If the patient is to receive tPA, then the blood pressure should be maintained below 185/110. If there are no contraindications to the use of beta-blockers, then labetalol or esmolol would be appropriate choices. Captopril sublingually or intravenous enalapril would be acceptable alternatives. Nitroglycerine or nitroprusside should be generally avoided due to their potentially negative effects on cerebral autoregulation. Calcium-channel blockers should also be avoided, especially if given sublingually. The aim should be to decrease the BP the minimum amount necessary since experimental data suggest any decrease in MAP of greater than 15% is accompanied by decreased blood flow to the Ischemic Penumbra.

2) If the patient is not to receive tPA then the threshold to treat hypertension should be fairly high for fear of decreasing perfusion pressure and blood flow to the ischemic penumbra. Avoid decreases greater than 15% of the MAP and when in doubt always err on the side of a higher rather than lower BP.

3) The majority of patients with hypertension associated with acute ischemic stroke will revert back to their premorbid level of BP within 24 hours. The first response to hypertension should be to minimize anxiety and causes of pain and discomfort such as positioning and urinary retention. It is important to remember that increased intracranial pressure may also be a cause of hypertension.

4) If the MAP is greater than 140 – 145, SBP > 220, or DBP > 120 on two readings 10 minutes apart, then use Labetalol 10 mg iv to cautiously reduce BP. Avoid dropping MAP by greater than 15%.

5) If the blood pressure is lower than these ranges, then emergency antihypertensive therapy should be deferred in the absence of left ventricular failure, aortic dissection, or acute myocardial ischemia.

6) If blood pressure is lowered by antihypertensive agents in the setting of acute stroke, serial neurological examinations should be performed to look for signs of deterioration such as increasing weakness or reduced level of consciousness.

7) Blood pressure that is substantially below the patient’s premorbid level should be treated with intravenous fluid boluses if there are signs of hypovolemia, and/or pressor agents.

Hemorrhagic Stroke

1) As there is no evidence that lowering systemic blood pressure decreases the incidence of rebleeding or cerebral edema, and some evidence that lowering systemic blood pressure in hemorrhagic stroke may be harmful, it is preferable to err on the side of not treating hypertension when in doubt.

2) If the MAP is greater than 140 – 145 mmHg, or there are signs of left ventricular failure, aortic dissection, or acute myocardial ischemia, then blood pressure should be lowered cautiously.

3) If the BP is to be reduced, it should be done cautiously to a MAP of 140 to 145.

Subarachnoid Hemorrhage

1) In SAH with a suspected cerebral aneurysm that is not yet clipped, the arbitrary goal is to reduce blood pressure to a level of 160/100.

2) The choices of antihypertensive agent would be the same as for ischemic CVA or ICH

3) Blood pressure should be reduced cautiously. Aim to decrease MAP by no more than 15% at a time and observe the patient closely for signs of neurologic deterioration secondary to lowering of BP.

References

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